A general problem in chromatography, adsorption processes, heterogeneous catalysis etc where porous particles are used, is that the mass transport rate is strongly dependent on the particle size. Rapid mass transport can be achieved by decreasing the particle size, but small particles will also increase the backpressure of the packed beds. Hence, a trade-off must be made between the mass transport rate and the pressure-flow properties. One way to improve the mass transport in a porous particle is to introduce a hierarchical pore structure, where large feeder pores from the particle surface open into a network of smaller pores with a large surface available for adsorption.
EP 0 222 718 (Mosbach and Nilsson) relates to particles that are used e.g. in chromatography or as microcarriers in the cultivation of anchorage dependent cells. EP 0 222 718 attempts to solve the mass transport problem by introducing cavities in the particles. More specifically, EP 0 222 718 discloses a method, wherein a cavity generating compound is added to an aqueous solution comprising a matrix material, emulsifier is added, particles are formed by dispersion and finally said cavity generating compound is washed out to leave behind cavities in the particles. An illustrative amount of cavity generating compound added is up to 10% by weight, corresponding to 3.6% by volume. This low amount of cavity-forming particles will not make contact with each other, resulting in a closed-cell porous structure as pointed out in EP 631 597. Accordingly, this is not a true hierarchical pore structure.
U.S. Pat. No. 5,739,021 (Katinger et al) discloses the formation of porous carriers suitable for cell culture. More specifically, such porous carriers are formed by mixing solid pore-forming agents into a polyolefin melt, which is then extruded into an aqueous phase through rotating knives to cut the extruded thread and form lenticular shaped particles. The pore-forming agents, which are normally water-soluble inorganic salts, are then removed by washing out according to conventional procedures. The melt formed as described above is of such an extreme viscosity, that extrusion technology must be used. However, such technology includes certain drawbacks, such as a practical limitation of the size of the particles formed. For example, in the field of chromatography, sizes of below about 200 μm diameter are usually desired. By extrusion, it is difficult to make particles within that size range.
M Zhang et al (M Zhang, Y Sun: J Chromatogr A 922, 77–86 (2001), Cooperation of solid granule and solvent as porogenic agents—Novel porogenic mode of biporous media for protein chromatography) teach a method wherein glycidyl methacrylate, divinylbenzene and triallylisocyanurate are bulk copolymerised in the presence of a cyclohexanol-dodecanol mixture as a porogen and sodium sulphate particles. The porogen and sodium sulphate are washed out and the polymer is crushed, resulting in particles of a hierarchical pore structure. One drawback with this technology is that it produces irregular particles, which are notoriously difficult to pack e.g. in a chromatographic column.
EP 0 631 597 (Larsson) describes preparation of agarose beads templated by oil droplets inside the agarose solution droplets, i.e. an oil-in-water-in-oil double emulsion system. One drawback of such a system is that the unstable nature thereof renders it very difficult to use in a production process. Another drawback is that due to a large volume fraction of superpores in the beads so produced, only low adsorption capacities are obtained when the beads are used in chromatography. Furthermore, said EP 0 631 597 is limited to agarose beads.
WO 0017257 (Berg et al) teaches an improvement over the above mentioned EP 0 631 597, wherein a polymeric water-in-oil emulsifier is used to make the double emulsion more stable and enable production on a larger scale. However, this technology will also exhibit the above mentioned problems related to the large volume fraction of superpores. In addition, this method is also limited to polysaccharides.
Accordingly, the various methods suggested in the prior art still suffer from essential drawbacks and limitations. Thus, there is still a need of improved methods for the production of porous beads.